Endocrine System & Anesthesia (Student Notes) PDF

The Endocrine System & Anesthesia Jordan Popp, DNP, CRNA, APRN 1  Overview Body homeostasis is controlled by 2 regulating systems: Nervous System Endocrine/Hormonal System Organs t...

The Endocrine System & Anesthesia Jordan Popp, DNP, CRNA, APRN 1  Overview Body homeostasis is controlled by 2 regulating systems: Nervous System Endocrine/Hormonal System Organs that secrete hormones = Endocrine glands The purpose of the endocrine system is regulation of behavior, growth, metabolism, fluid and electrolyte status, development, and reproduction. Endocrine glands secrete hormones directly into surrounding ECF. Exocrine glands secrete their products through ducts. Body homeostasis is controlled by two regulatory systems: the nervous system and the endocrine hormonal system. Organs that secrete hormones are called endocrine glands. Examples would be the pituitary gland, thyroid gland, parathyroid glands, adrenal glands, pancreas, ovaries, testes and the placenta. The purpose of the endocrine system is regulation of behavior, growth, metabolism, fluid and electrolyte status, development and reproduction. Endocrine glands secrete hormones directly into surrounding extracellular fluid. Exocrine glands, on the other hand, secreted their products through ducts. Examples would be the salivary and sweat glands. 2  Hormones Signaling molecules or chemical messengers that transport information from one set of cells to another Endocrine Function Transmission of a hormonal signal through the blood stream to a distant target cell Paracrine Function A hormone that signals act on a neighboring cell of a different type Autocrine Function The secreted hormone acts on the producer of the cell itself Cytokines are peptides secreted by cells that can serve as autocrine, paracrine, or endocrine. Hormones are signaling molecules, or chemical messengers, that transport information from one set of cells to another. Endocrine function is transmission of hormonal signal through the bloodstream to a distant target cell. Typically, they travel through the blood circulation. Paracrine Function, a hormone that’s signal acts on a neighboring cell of a different type. And then Autocrine is a hormone that secretes hormones that act on the precursor cell itself. Cytokines are peptides secreted by cells that can serve as autocrine, paracrine, or endocrine. Examples of an endocrine function would be the pituitary gland to secrete hormones that act on the adrenal glands, whereas a paracrine function, would be the pancreas, alpha cells to the acting on the pancreas again, the beta cells. 3  Hormones can be classified into 3 major categories 1. Proteins or Peptides Hormones 2. Tyrosine Amino Acid Derivatives 3. Steroids So hormones can be classified into three categories, first of which being proteins or peptides. Second is tyrosine amino acid derivatives, and third, steroids. 4  Water-soluble peptide or have a protein structure Synthesized in endocrine cells as pre-hormones and pro- hormones Hormones: Processed and stored in secretory glands until needed Peptide or Stimulus to secretion causes exocytosis of the hormone into the ECF Protein Examples: Insulin, growth hormone (GH), vasopressin (antidiuretic hormone [ADH]), angiotensin, prolactin, erythropoietin, calcitonin, somatostatin, adrenocorticotropic hormone (ACTH), oxytocin, glucagon, and parathyroid hormone (PTH). The first of the hormones that we're going to talk about is a peptide or protein hormones They are water soluble peptide, or have a protein structured. They're synthesized in endocrine cells as pre hormones and pro hormones. They are processed and stored in secretory glands until needed. Stimulus to secretion causes exocytosis of the hormone into the extracellular fluid. Examples you can see listed there, some of the bigger ones include insulin, growth hormone, ADH, ACTH, parathyroid hormone and oxytocin. 5  Hormones: Tyrosine Derived from the amino acid tyrosine Amino Acid Thyroid hormones (thyroxine and Triiodothyronine) Stored in the thyroid Derivative Catecholamines (Dopamine, Epi, and Norepi) Stored in the adrenal medulla The second category is the tyrosine amino acid derivatives derived from the amino acid tyrosine. The biggest ones are the thyroid hormones stored in the thyroid. And then catecholamines, which are dopamine, Epi and Norepi; which are stored in the adrenal medulla, which we'll discuss more in detail later on in the lecture. 6  Lipid soluble, derived from cholesterol or structurally similar to cholesterol Examples: Cortisol & Aldosterone Hormones: Stored in the adrenal cortex Steroid Estrogen, Progesterone, & Testosterone Active metabolites from Vitamin D Steroid hormones are NOT stored in discrete secretory granules but are compartmentalized within the endocrine cell and released into the extracellular fluid by simple diffusion through the cell membrane into the blood Final category of hormones would be the steroid hormones. They are lipid soluble derived from cholesterol or structurally similar to cholesterol. Examples would be cortisol and aldosterone, which both of which are stored in the adrenal cortex. Other examples estrogen, progesterone, testosterone and active metabolites from vitamin D. Important to note here that steroid hormones are not stored in secretory granules, but are compartmentalized within the endocrine cells and released into the extracellular fluid by simple diffusion through the cell membrane into the blood. This is possible because they are lipid soluble. 7  Most catecholamines and protein hormones are water soluble and circulate freely unbound to carriers Steroids and thyroid hormones are bound to transport proteins Protein binding helps protect the hormones from Hormone metabolism and renal clearance The half-life of steroid and thyroid hormones is typically Transport much longer due to binding Example: Thyroid hormone is 99% protein bound half life = 1-6 days Insulin is not protein bound half life = 7 min Now looking at how these hormones are transported. Most catecholamines and protein hormones are water soluble and circulate freely, unbound to any carriers. Steroid and thyroid hormones are bound to transport proteins. The protein binding helps protect the hormones from metabolism and renal clearance. The half life of steroid and thyroid hormones is typically much longer due to binding. Below, I have listed that the thyroid hormone is 99% protein bound with a half life of 1-6 days, whereas insulin, which is not protein bound, has a half life of only 7 minutes. 8  Hormone Receptor Activation Hormone Receptor Locations 1. On the surface of the target cell membrane Protein, peptide, and catecholamine hormone receptor sites 2. In the target cell cytoplasm Steroid 3. In the target cell nucleus Thyroid Hormone binding to a cell membrane receptor triggers a response by activating enzyme systems in or near the plasma membrane bilayer The activated enzyme generates intracellular signals (Second messengers) which care the hormone’s message within the intracellular space Once the hormone reaches its potential site where it's going to have its action, it has three potential locations that can be. On the surface of the target cell membrane, which would be where your proteins, peptides and catecholamine hormone receptor sites are. In the target cell cytoplasm, which will be where your steroid is, or all the way through into the cell nucleus, which is where the thyroid hormones act. Hormone binding to a cell membrane triggers a response by activating enzyme systems in or near the plasma membrane bilayer. The activated enzyme generates inner cellular signals, which is known as second messengers, which carry the hormone signal within the intracellular space. 9 Gland/Tissue Hormones Major Functions Chemical Structure Hypothalamus Thyrotropin-releasing hormone Stimulates secretion of TSH and prolactin Peptide Corticotropin-releasing hormone Causes release of adrenocorticotropic hormone Peptide Growth hormone-releasing hormone Causes release of growth hormone Peptide Growth hormone inhibitory hormone Inhibits release of growth hormone Peptide (somatostatin) Gonadotropin-releasing hormone Causes release of luteinizing hormone and follicle-stimulating hormone Peptide Dopamine or Prolactin-inhibiting factor Inhibits release of prolactin Amine Anterior Growth hormone Stimulates protein synthesis and overall growth of most cells and tissues Peptide Pituitary Thyroid-stimulating hormone Stimulates synthesis and secretion of thyroid hormones (thyroxine and triiodothyronine) Peptide Adrenocorticotropic hormone Stimulates synthesis and secretion of adrenocortical hormones Peptide Prolactin Promotes synthesis and secretion of adrenocortical hormones Peptide Follicle-stimulating hormones Causes growth of follicles in the ovaries and sperm maturation in Sertoli cells of testes Peptide Luteinizing hormone Stimulates testosterone synthesis in Leydig cells of testes; stimulates ovulation, formation of corpus luteum, and estrogen Peptide and progesterone synthesis in ovaries Posterior Antidiuretic hormone (vasopressin) Increases water reabsorption by the kidneys and causes vasoconstriction Peptide Pituitary Oxytocin Stimulates milk ejection from breasts and uterine contraction Peptide Thyroid Thyroxine (T4) & Triiodothyronine (T3) Increases the rates of chemical reactions in most cells, thus increasing body metabolic rate Amine Calcitonin Promotes deposition of calcium in the bones and decreases extracellular fluid calcium ion concentration Peptide Adrenal Cortex Cortisol Multiple metabolic functions for controlling metabolism of proteins, carbohydrates, and fats; also has anti-inflammatory Steroid effects Aldosterone Increases renal sodium reabsorption, potassium secretion, and hydrogen ion secretion Steroid Adrenal Norepinephrine & Epinephrine Same as sympathetic stimulation Amine Medulla This slide and the next slide is made up of all the different glands and tissues where hormones are produced; the hormones that they release, the functions of each of the hormones, as well as the chemical structure. I think it'd be smart for you to spend some time categorizing these, getting to know them, we will talk about a lot of them. However, you just need to commit a lot of these to memory and really paying attention on what kind of chemical structure that they are. 10 Gland/Tissue Hormones Major Functions Chemical Structure Pancreas Insulin (Beat cells) Promotes glucose entry in many cells, and in this way controls carbohydrate metabolism Peptide Glucagon (alpha cells) Increases synthesis and release of glucose from the liver into the body fluids Peptide Parathyroid Parathyroid hormone Controls serum calcium ion concentration by increasing calcium absorption by the gut and kidneys and releasing calcium from Peptide bones Testes Testosterone Promotes development of male reproductive system and male secondary sexual characteristics Steroid Ovaries Estrogens Promotes growth and development of female reproductive system, female breasts, and female secondary sexual characteristics Steroid Progesterone Stimulates secretion of “uterine milk” by the uterine endometrial glands and promotes development of secretory apparatus of Steroid breasts Placenta Human chorionic gonadotropin Promotes growth of corpus luteum and secretion of estrogens and progesterone by corpus luteum Peptide Human somatomammotropin Probably helps promote development of some fetal tissues, as well as the mother’s breasts Peptide Estrogens Promotes growth and development of female reproductive system, female breasts, and female secondary sexual characteristics Steroid Progesterone Stimulates secretion of “uterine milk” by the uterine endometrial glands and promotes development of secretory apparatus of Steroid breasts Kidney Renin Catalyzes conversion of angiotensinogen to angiotensin I (acts as an enzyme) Peptide 1,25-dihyroxycholecalciferol Increases intestinal absorption of calcium and bone mineralization Steroid Erythropoietin Increases erythrocyte production Peptide Heart Atrial natriuretic peptide Increases sodium excretion by kidneys, reduces blood pressure Peptide Stomach Gastrin Stimulates hydrogen chloride secretion by parietal cells Peptide Small Intestine Secretin Stimulates pancreatic acinar cells to release bicarbonate and water Peptide Cholecystokinin Stimulates gallbladder contraction and release of pancreatic enzymes Peptide Adipocytes Leptin Inhibits appetite, stimulates thermogenesis Peptide 11  Peptide and Catecholamine Hormone Cell Activation Hormones that use cAMP as their 2nd Messenger: TSH Vasopressin (V2 receptor) ACTH PTH Glucagon Catecholamines (beta receptors) FSH LH Several different second messenger systems operate in response to cell membrane receptor hormone binding. The most widely described second messenger system is the cyclic adenosine monophosphate, which is known as a C amp, or some people call the cyclic AMP system. This is most commonly used for peptides and catecholamine hormones. So to start, the transduction mechanism is initiated when a hormone, which you can see up there is the first messenger up on top, occupies a G protein associated receptor, which is kind of that purplish blob on the left receptor, and activates the plasma membrane enzyme, adenosyclase. The membrane bound adenosyclase then catalyzes the inner cellular conversion of adenosine triphosphate to cAMP. cAMP, in turn becomes the hormones intracellular messenger, activating intracellular enzymes, modifying cell membrane permeability or transport and altering cellular gene expression, overall. The enzyme phosphodiesterase catalyzes the hydrolysis of cAMP and terminates its inner cellular actions. Hormones that use the cAMP or cyclic AMP as a second messenger include, you can kind of see a list there. TSH, vasopressin (the V2 receptor), ACTH, PTH, glucagon, all the catecholamines, follicle stimulating hormone and the luteinizing hormone. 12  Thyroid & Steroid Cell “Activation” You can trust the peptide and catecholamine hormones that we talked about in the previous slide. Thyroid and steroid hormones produce the desired target cell response chiefly by interacting with specific intracellular hormone receptors. Thyroid and steroid hormones are small, lipophilic molecules that enter target cells by simple diffusion or by other special transport mechanisms. Once within the cell, these hormones occupy specific intracellular receptors. So first, let's look at the top image of the steroid hormone receptor. There you can see the steroid hormone receptors enter in and meet their receptor. The hormone meets its receptor in the cytoplasm. Down at the second picture that's depicting a thyroid hormone. Thyroid hormone receptors are predominantly in the target cell nucleus. So if you look on the side, you can see the t3 and t4 that actually go all the way through into the cell nucleus, where they finally meet their steroid receptor bonding site. In combination with these receptors, thyroid hormones interact with the DNA in the cell nucleus to enhance or suppress any kind of gene transcription or translation. Thyroid and steroid hormones cause target cells to either synthesize proteins such as enzyme or target proteins. 13  Hormone Hormones that act by binding to cell membrane receptors Onset & generate a hormonal effect in seconds to minutes Duration of peptide, protein, and catecholamine Hormones that bind to intracellular receptors and activate Action the transcription processes of specific genes may require several hours or even days to generate a hormonal response thyroid and steroid hormones Now looking at the onset and duration of action of the hormones acting on the receptor sites. Hormones that act by binding to the cell membrane receptors, which would be your peptide, protein, catecholamines, generate a hormonal effect that takes seconds to minutes to have an action. Hormones that bind to intracellular receptors and activate the transcription process of specific genes may require several hours or even days to generate a hormonal response. Those are the ones that go and have the receptors in either the cytoplasm or the nucleus, the thyroid or the steroid hormones. 14  Each hormone has 2,000-100,000 potential binding sites specific to it Receptors are constantly being destroyed and replaced ½ life of an insulin receptor is 7 hours Hormone The destruction and replacement my be natural or part of an acquired or genetic disease Receptor Hormone receptors are inversely related to the concentration of circulating hormones Regulation Down-Regulation Increased hormone level = decreased hormone receptors Up-Regulation Low circulating hormones may cause the target cell to increase receptors Each hormone has 2000-100,000 potential binding sites specific to it. Receptors are constantly being destroyed and replaced. The half life of an insulin receptor, for example, is only seven hours, which is crazy to think about in a 14-hour span, your receptor is completely gone and replaced. The destruction and replacement may be natural or part of an acquired or genetic disease. Hormone receptors are inversely related to the concentration of the circulating hormone, so you can have down regulation, which, if you have an increased hormone level, you're going to have decreased hormone receptors. Up regulation, on the other hand, is you'll have low circulating hormones, which may cause the target cell to increase the amount of receptors that it has. Some examples of down regulation: first one we'll talk about is insulin resistance and obesity and with T2 diabetics. When blood sugar levels of these patients are high, the body produces more insulin to try to lower them. However, over time, the cells become less sensitive to the insulin, and the number of insulin sectors just start to decrease. The next example is progesterone. Progesterone is a hormone that helps to prepare the uterus for pregnancy. However, if the levels of progesterone are too high, the cells in the uterus can become less sensitive to progesterone, and the number of progesterone receptors decrease. This can lead to complications during pregnancy, such as miscarriage or pre term labor. Receptors for other hormones that can also be a factor of down regulation are growth hormone, cortisol, thyroid hormone, can all be down regulated in response to 15 prolonged exposure to high levels of those specific hormones. Moving on to some examples of upregulation: Estrogen receptors in the uterus during pregnancy. So during pregnancy, the number of estrogen receptors in the uterus increase. This allows the uterus to become more sensitive to estrogen, which is necessary for the growth and development of the fetus. Another example of upregulation would be prolactin receptors in the breast during lactation. In preparation for lactation, the number of prolactin receptors in the breast are to increase. This allows the breast to become more sensitive to prolactin, which is necessary for milk production. 15  Hormone Secretion Regulation Synthesis & Secretion by endocrine glands are regulated by 3 control mechanisms: 1. Neural Controls Can evoke or suppress hormone secretion Pain, emotion, smell, touch, injury, stress, sight, and taste can alter hormone release Glucagon, cortisol, and catecholamines are all stimulated by the stress response to surgery and trauma. Deep general anesthesia or regional anesthesia blunts this stress response but does not eliminate it. 2. Biorhythms Governed by genetically encoded or acquired biorhythms. These intrinsic hormonal oscillations may be circadian, monthly, or seasonal Biorhythms also may vary at different stages of development and life 3. Feedback Mechanism (see next slide) Many endocrine disorders are caused by the breakdown of feedback loops The synthesis and secretion by endocrine glands are regulated by three different control mechanisms. First, you have your neural controls. They can evoke or suppress hormone secretion, pain, emotion, smell, touch, injury, stress, sight and taste, can alter hormones being released. Glucagon, cortisol and catecholamines are all stimulated by the stress response to surgery or trauma. Deep general anesthesia or regional anesthesia blunts that stress response, but does not completely eliminate it. Biorhythms governed by genetically encoded or acquired biorhythms, these intrinsic hormone oscillations may be circadian, monthly or seasonal. Biorhythms also may vary dependent on the stages of development of life. So if we're looking at this circadian 24-hours example, that would be the glucocorticoid secretion that your body goes through every day. Monthly, that would be more so in the lines of a menstrual cycle. Seasonal thyroxine production is lower in the winter and higher in the summer due to the amount of sunlight, temperature, and of course, your diet intake. And then stages of life would be an example of your growth hormone secretion, which is going to be obviously higher in your adolescence and then tapering off as you age. Feedback mechanism, we'll talk more on the next slide. Important to know that many endocrine disorders that we will be talking about are caused by the breakdown of these feedback loops. 16  Negative Feedback Hormone Regulation Negative feedback loops Act to limit or terminate the production and secretion of a given hormone once the appropriate response has occurred. Negative feedback from a target cell product to the hormone producer (the endocrine gland) limits or prevents hormone excess. When concentrations of the product are low, feedback inhibition to the endocrine gland is lessened and hormone secretion is enhanced. Important in the regulation of hormones of the hypothalamus and pituitary gland Virtually all hormones secreted from endocrine glands are controlled by some type of negative feedback mechanism. For example, parathyroid hormone is controlled by calcium. Insulin and glucagon are controlled by glucose, and vasopressin is controlled by serum osmolality. The negative feedback mechanism is a very important system for the regulation of hormones of the hypothalamus and pituitary gland. Hypothalamic hormones stimulate the release of pituitary hormones from the pituitary gland. The pituitary hormones, in turn, may stimulate an output of product from the peripheral target cells that they specifically act on. Then in turn, the product from the peripheral target cells may initiate feedback to the pituitary gland or the hypothalamus, or in some cases, both of which to inhibit pituitary and hypothalamic hormone synthesis and discharge that would allow them to release more hormones. 17  Positive Less common A given hormone response initiates signals amplifying more of Feedback its own release Hormone Example The surge in LH that precedes ovulation is stimulated by Regulation LH Oxytocin release during childbirth Positive feedback is less common. Hormone regulating mechanism in which a given hormone response initiates signaling amplification of more hormone release. The surge in luteinizing hormone that produces ovulation is stimulated by luteinizing hormone. Another one is oxytocin is a hormone that is released during childbirth. It causes the uterus to contract, which helps to push the baby out. The contraction of the uterus itself releases more oxytocin, which then causes more contraction. That is an example of a positive feedback loop which continues over and over again until the baby is born. 18  Pituitary Gland “Master Endocrine Gland” 500mg in weight and the size of a pea Located at the base of the brain enclosed within a bony cavity of the sphenoid bone called the sella turcica The pituitary is connected to the overlaying hypothalamus by the hypophysial stalk (pituitary stalk) The hypothalamus is located below the thalamus, behind the optic chiasm, and between the optic tracts. The hypothalamus collects and integrates information from varies parts of the body and uses this information to control the secretion of vital pituitary hormones The pituitary is divided into an anterior and posterior lobe The first gland we're going to talk about is the pituitary gland, which is also known as the master endocrine gland. It is only 500 milligrams in weight and is actually only the size of a pee. It is located at the base of the brain, enclosed within a bony cavity of the sphenoid bone called the sella turcica. The Pituitary is connected to the overlain hypothalamus by the hypophysial stock, or pituitary stock. The hypothalamus, as the name implies, is located below the thalamus, behind the optic chiasm, and between the optic tracts. The hypothalamus collects and integrates information from various parts of the body and uses this information to control the secretion of vital hormones from the pituitary. The Pituitary is divided into an anterior and posterior lobe, which we'll go into more detail in the next slides. 19  Anterior Pituitary Lobe Makes up 80% of the pituitary gland weight Secretes 6 peptide hormones Growth Hormone (somatotropin) Corticotropin or ACTH Thyroid-stimulating Hormone (thyrotropin) Follicle-stimulating Hormone Luteinizing Hormone Prolactin First, let's look at the anterior pituitary lobe. It makes up approximately 80% of the pituitary gland weight, and secretes six main peptide hormones. We’ll go over each of these in a little more detail. Growth hormone, also known as somatotropin, promotes skeletal development and body growth. It also stimulates insulin like growth factor 1 (IGF 1) from the liver. It inhibits actions of insulin on carbohydrate and fat metabolism. Corticotropin or ACTH, regulates the growth of the adrenal cortex and stimulates the release of cortisol and adrenergic hormones. Thyroid stimulating hormone, as the name implies, controls the growth and metabolism of the thyroid gland and the secretion of the thyroid hormones. Follicle stimulating hormone, stimulates ovarian follicle development in females and spermatogenesis in males. Luteinizing hormone induces ovulation and corpus luteum development in females and stimulates the testes to produce testosterone in males. Prolactin promotes mammary gland development and milk production in the breasts. Prolactin also exerts an effect on reproductive function by inhibiting the synthesis and secretion of follicle stimulating hormone and the luteinizing hormone. Prolactin synthesis is markedly increased during pregnancy. 20  Control of Anterior Pituitary Hormone Secretion Synthesis of anterior pituitary hormones is controlled by signals from the hypothalamus Hypothalamic neurohormones are released into a capillary bed of the hypothalamus (median eminence) The hypothalamic hormones travel from the capillary plexus of the median eminence, down the pituitary stalk, in a specialized vascular system called the hypothalamic-hypophysial portal vessels At the anterior pituitary lobe, the hypothalamic hormones are released in high concentrations into capillary sinuses located among the glandular cells. The hypothalamic hormones then locate and bind to their specific target cell type Hormones have either an inhibitory or a stimulatory effect Now let's take some time to look at how hormones are controlled and secreted or inhibited from the anterior pituitary. Synthesis of anterior pituitary hormones is controlled by signals from the hypothalamus. Hypothalamic neurohormones are released into the capillary bed of the hypothalamus, and you can look over at the image on the right hand side, as I kind of go through this looking at the median eminence. The hypothalamic hormones travel from the capillary Plexus of the medium eminence down the pituitary stock in a specialized vascular system called the hypothalamic hypophyseal portal vessels. At the anterior pituitary lobe, the hypothalamic hormones are released in high concentrations into capillary sinuses located among the glandular cells. The hypothalamic hormones then locate and bind to specific target cell types. Hormones have either inhibitory or stimulatory effect. 21 The following chart is the hypothalamic hormones and corresponding anterior pituitary hormones that are then released. A lot of the hypothalamic releasing inhibitory hormones have very similar names to the hormones that are then released or inhibited from the anterior pituitary. So take a look at this chart. Read it over. A lot of it just makes sense based on word association, but take some time to look at it. 22  Anterior Pituitary Disorders - Hyposecretion Decreases in thyroid function due to reduction in TSH Decrease of cortisol production by the adrenal cortex due to low ACTH levels Suppression of sexual development and reproductive function Surgical patients with hypopituitary disorders should be ready to be treated for increased intracranial pressure. Consider hormone replacement, especially thyroid and cortisol replacement Due to risk of DI (low ADH) after removal of the tumor, vasopressin should be available. Looking now at the anterior pituitary disorders. First we're going to look at the hypopituitarism, or hypo secretion, includes: decreases in thyroid function (due to reduction in levels of the thyroid stimulating hormone), depression of cortisol production by the adrenal cortex (due to lowering of the ACTH levels), suppression of sexual development and reproduction function (due to deficient gonadotropic hormone secretion). Surgical patients with acute hypopituitary disorders may require treatment of increased intracranial pressure and consideration of hormone replacement, especially thyroid and cortisol replacement. Because of the possibility of diabetes insipidus after removal of the tumor, vasopressin should be available in the OR to administer. 23  Anterior Pituitary Disorders-Hypersecretion Most pituitary tumors are benign hypersecreting pituitary adenomas The three most common hypersecreting pituitary tumors are those that produce Prolactin ACTH GH Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Galactorrhea, amenorrhea, and infertility in women Diminished libido and infertility in men Treated by dopamine agonists So looking at anterior pituitary disorders that have hyper secretion. Most pituitary hormones are benign, hyper secreting pituitary adenomas. The three most common hyper secreting pituitary tumors are those that produce prolactin, ACTH or growth hormone. Tumors that secrete gonadotropin and thyrotropin hormones are pretty rare. Preparation for pituitary surgery is guided by the results of a preoperative neurologic and endocrine test, hormone blood work, and, of course, a radiographic examination of the skull. Hyper secreting pituitary tumors are usually micro adenomas. Less commonly, pituitary tumors become large and compress and destroy some of the neighboring cells, producing a deficiency in hormones from surrounding anterior pituitary cells. Hyperprolactinemia is a common pituitary hormone hypersecretion syndrome in both men and women. Prolactin secreting tumors commonly produce symptoms of galactorrhea, amenorrhea and infertility in women and diminished libido and infertility in men. Dopamine agonists are used to control prolactin levels, decrease tumor size and restore normal gonadal functions. Patients who have a suboptimal response to medical therapy may benefit from micro surgery-removal of the pituitary tumor. 24  GH-secreting cells constitute up to 50% of the total anterior pituitary cell population GH (somatotropin) is synthesized and secreted by somatotrope cells which are under complex control by the hypothalamus and peripheral factors GH-releasing hormone from the Growth Hormone hypothalamus stimulates GH release GH-inhibiting hormone from the hypothalamus inhibits GH release GH secretion increases as we age, plateaus in adulthood then declines Growth hormone secreting cells, also known as somatotrope cells, constitute up to 50% of the total anterior pituitary cell production. Somatotrope is synthesized and secreted by somatotrope cells, and is under complex control by the hypothalamus and other peripheral factors. Growth hormone releasing hormone from the hypothalamus stimulates growth hormone release, and likewise, growth hormone inhibiting hormone (somatostatin) also from the hypothalamus, inhibits growth hormone release. In addition, growth hormone secretion is stimulated by stress, trauma, hypoglycemia, strenuous exercise and deep sleep. The growth hormone secretion rate is generally increased in childhood, followed by a further increase in adolescence, a plateau in adulthood and then a decline as we age. The normal physical decline associated with aging may be due in part to an age related decline in growth hormone production. So makes you wonder if maybe, if we had continuous growth hormone, would we just live and grow forever. 25  Growth Hormone Unlike other APH, GH does not exert its principal effects through a specific target gland but functions through all or almost all tissues of the body A major target of GH is the liver, where it stimulates the production of somatomedin C (IGF-1) Skeletal muscle, the heart, skin, and visceral organs undergo hypertrophy and hyperplasia in response to GH and somatomedins Most obvious effect of GH is on the skeletal muscle frame Under the influence of GH, osteoblasts are stimulated Bones elongate at the epiphyseal plate, skeletal frame enlarges, after puberty, the growth plates unite with the shaft of the bone, GH has no further capacity to increase bone length Unlike other anterior pituitary hormones, growth hormone does not exert its principal effects through a specific target gland, but functions through all, or almost all, tissues of the body. Growth Hormone promotes the growth and development of most tissues that are capable of growing. A major target of growth hormone is the liver, where it stimulates the production of Somatomedin C, also called IGF-1, which, if you remember back a couple slides we talked about that being insulin like growth factor one. Somatomedin C and other Somatomedin’s mediate many of growth hormones effects. Skeletal muscle and heart, skin, visceral organs undergo hypertrophy and hyperplasia in response to growth hormone and Somatomedins. The most obvious effect of growth hormone is on the skeletal frame. It produces linear bone growth by stimulating the epiphyseal cartilage, or growth plate at the ends of the long bones. Throughout childhood, under the influence of growth hormone bone forming cells called osteoblasts, are stimulated. Bones elongate at the epiphyseal cell and the skeletal frame elongates. After puberty, the growth plates unite with the shaft of the bone, bone lengthening stops, and growth hormone has no further capacity to increase bone length. So bad news for anyone hoping to get a little bit taller-since we're past puberty and those growth plates have united, taking growth hormone to stimulate osteoblasts would not actually make you taller. 26  Growth Hormone GH & IGF-1 support growth by increasing amino acid transport into cells and enhancing protein synthesis in the cell GH decreases the catabolism of existing proteins by stimulating lipolysis and mobilizing free fatty acids for energy use GH is a diabetogenic hormone It increases blood glucose levels by decreasing the sensitivity of cells to insulin and inhibiting glucose uptake into cells Subject to negative feedback control GH and IGF-1, exert negative feedback control on the pituitary and hypothalamus GH release is also inhibited by hyperglycemia and increased plasma free fatty acids Growth hormone and IGF-1 support growth by increasing amino acid transport into cells and enhancing protein synthesis in the cell. Growth Hormone also decreases the catalysm of existing proteins by stimulating lipolysis and mobilizing free fatty acids for energy use, which is a protein sparing effect. In addition to its growth promoting activities, growth hormone is said to be a diabetogenic hormone. It increases blood glucose levels by decreasing the sensitivity of cells to insulin, which would promote insulin resistance and inhibiting glucose uptake into cells. As is true with other anterior pituitary hormones, growth hormone secretion is subject to negative feedback control. Growth Hormone as well as IGF-1 exert negative feedback control on the pituitary and hypothalamus. Growth hormone release is also inhibited by hyperglycemia and increased plasma free fatty acids. 27  Growth Hormone - Hyposecretion GH deficiency in childhood results in dwarfism Insufficient bone maturation = short stature. Mild obesity Decreased lean body mass Hypoglycemia Delayed puberty Symptoms of GH deficiency may be the result of: Hypothalamic dysfunction, pituitary disease, failure to generate normal insulin growth factor hormones, or GH-receptor defects Growth hormone hyposecretion. Deficient growth hormone production in childhood can result in insufficient bone maturation and short stature, which is a condition known as dwarfism. Mild obesity, decreased lean body mass and hypoglycemia are common in people who are receptive to growth hormone deficiencies. Puberty is usually delayed in these people. Symptoms of growth hormone deficiency may be the result of hypothalamic dysfunction, pituitary disease, failure to generate normal insulin growth factor hormones or growth hormone receptor defects, whereas it isn't an issue with the growth hormone itself- it's an issue with a number of receptors. The biosynthesis of human growth hormone by recumbent DNA technology has enhanced the outlook of these patients for those that suffer from growth hormone deficiency. 28  Growth Hormone - Hypersecretion Hypersecretion of GH is usually caused by a GH-secreting pituitary adenoma (99% of cases) leading to acromegaly in adults Acromegaly is produced by the excessive action of GH and IGF-1 after adolescence, leading to anatomic changes and metabolic dysfunction If hypersecretion of GH occurs before puberty, all body tissues grow and the individual grows very tall (8-9 ft), this is known as gigantism Looking now at hypersecretion of growth hormone. Approximately 15% of all pituitary tumors release excess growth hormone. Hypersecretion of growth hormone is usually caused by a growth hormone secreting pituitary adenoma, which is about 99% of cases, producing a highly distinctive syndrome in adults called acromegaly. Acromegaly is produced by an excessive action of growth hormone and IGF- 1 after adolescence, leading to anatomic change in changes and metabolic dysfunction. If hypersecretion of growth hormone occurs before puberty, that is before closure of those growth plates, all body tissues grow, and the individual grows very tall. We're talking like 8 to 9 feet, an extremely rare condition known as gigantism. 29  Growth Hormone - Hypersecretion Recall that growth plates close with adolescence, the excessive production of GH associated with acromegaly enhances the growth of periosteal bone by the stimulatory effect of GH on bone osteoblasts Periosteal growth causes new bones to be deposited on the surface of existing bones Massive thick bones Bones of the hands and feet double in size Acromegaly is diagnosed most often in adults in their 40s and 50s However, the disease is present earlier, just slow progressing Because growth plates close with adolescents, the excess production of growth hormone associated with acromegaly does not induce bone length, but rather enhances the bone growth of peristyle bone by the stimulatory effects of growth hormone on osteoblasts. Periosteal growth causes new bone to be deposited on the surface of existing bone. The increased bone growth in patients with acromegaly produces bones that are massive in size and thickness. Bones of the hands and feet become particularly large, almost twice the size as a normal hand or foot. Acromegaly is diagnosed most often in adults in their 40s and 50s. But the disease is slowly progressive and is usually present for years preceding the diagnosis. 30  Growth Hormone - Hypersecretion Soft tissues are also affected with GH hypersecretion Coarsened facial features that include large bulbous nose, supraorbital ridge overgrowth, dental malocclusion, and prominent prognathic mandible Changes in appearance are insidious and treatment is not sought until the disease is advanced Thickening of the skin may make IV insertion challenging The liver, heart, spleen, and kidneys become enlarged. Baseline echocardiography is indicated. Glucose intolerance is commonly seen Effects of the expanding tumor may include headaches and visual field defects Significant increases in intracranial pressure are uncommon. Compression or destruction of normal pituitary tissue by the tumor may eventually lead to panhypopituitarism. Soft tissue changes are also prominent with growth hormone hypersecretion. Patients develop coarsened facial features that include a large bulbous nose, super orbital rich overgrowth, misaligned teeth and protruding mandibles. The changes in appearance are insidious, and many patients do not seek treatment until the diagnosis is obvious and the disease course is further along. Thick and coarse skin may become apparent when inserting IV catheters and may lead to difficult IV catheter placement. The liver, heart, spleen and kidneys become enlarged. Cardiomyopathy and hypertension in patients with acromegaly can lead to symptomatic cardiac disease such as diastolic dysfunction and heart failure. Hypertension occurs in more than 40% of patients, and evidence of left ventricular hypertrophy is common. A baseline echocardiogram is indicated for all patients with hypersecretion of growth hormone in preop. The insulin auto antagonist effects of growth hormone produce glucose intolerance in most patients and diabetes in up to 25% of patients with acromegaly. Clinical manifestations resulting from the local effects of the expanding tumor may include headaches and visual field defects. Significant increase in intracranial pressure is uncommon for the most part. Compression or destruction of normal pituitary tissue by the tumor may eventually lead to panhypopituitarism. 31  Growth Hormone - Hypersecretion Common Features of Acromegaly Skeletal overgrowth Soft tissue overgrowth Visceromegaly Hypertension Osteoarthritis Glucose intolerance Peripheral neuropathy Skeletal muscle weakness Extrasellar tumor extension Common features of acromegaly include skeletal muscle overgrowth, enlarged hands and feet, prominent mandibles, soft tissue overgrowth, which would be the appearance of enlarged lips, tongues, epiglottis and distorted facial features, visceral megaly-which is the enlargement of your abdominal organs, such as your swing kidney, liver, hypertension, osteoarthritis, glucose intolerance, peripheral neuropathy, skeletal muscle weakness and any extracellular tumor extension, which would be any kind of growth outside of the stelatricia of the tumor would include symptoms of headaches and visual field defects. 32  Growth Hormone - Hypersecretion Treatment for acromegaly is aimed at restoring normal GH levels through surgical, pharmacologic, and radiotherapeutic approaches. Hormonal control has a beneficial impact on survival. Lowering serum GH levels results in reduction of the mortality rate. The preferred initial therapy, especially for small, adenomas, is microsurgical removal of the pituitary tumor, with preservation of the gland. The surgical approach to the pituitary tumor is most often via the transsphenoidal route, and this method is generally well tolerated by most patients. For transsphenoidal pituitary surgery, the head of the bed is typically elevated 15 degrees to improve venous drainage. Venous air embolism is usually not a concern unless there is cavernous sinus invasion by the tumor and the patient is positioned in a steep head-up tilt. The approach and exposure of the tumor are not usually associated with significant blood loss. An anesthetic technique that incorporates muscle relaxation and allows for smooth extubation and rapid neurologic assessment is desirable. The patient should be prepared preoperatively for awakening with nasal packing. Surgical complications are not common but may include epistaxis, transient DI, cranial nerve damage, hyponatremia, and cerebral spinal fluid leaks. Administration of octreotide or lanreotide (somatostatin receptor ligands), cabergoline (a dopamine agonist), pegvisomant (a GH-receptor antagonist), and gland irradiation may be used for tumor regression or as treatment options for patients who are not surgical candidates. If untreated, acromegaly is associated with decreased life expectancy, with cardiac, cerebrovascular and respiratory complications being the most common causes of death. Treatment for acromegaly is usually aimed at restoring normal growth hormone levels through surgical, pharmacological or radiotherapeutic approaches. Hormonal control has a beneficial impact on survival. Lowering serum growth hormone levels results in reduction of the mortality rate. The preferred initial therapy is micro surgical removal of the pituitary tumor with preservation of the gland itself. Surgery achieves biochemical cure in 70 to 90% of micro adenomas and approximately 50% remission of macro adenomas. The surgical approach in the pituitary tumor is most often via the transphenoid route, and this method is generally well tolerated by most patients. The transcranial surgical approach is usually reserved for very large tumors with supercellular extension. For transphenoid pituitary surgery, the head of the bed is typically elevated 15 degrees to improve venous drainage. It's not wrong of you to immediately start thinking about venous air embolism. That's a normal thought. However, it's usually not a concern unless the cavernous sinus is invaded by the tumor and since the patient is not in a steep head of position of 15 degrees, is usually fine. The approach and exposure of the tumor are not usually associated with that significant of a blood loss. An anesthetic technique that incorporates muscle relaxation and allows for smooth extubation with a very rapid neurological assessment is the goal. Typically, 33 these patients they like to see them extubated in the OR and are able to pretty much immediately perform a neurological assessment right there. The patient should be prepared preoperatively for awakening with nasal packing in place. Surgical complications are not common, but they may include a bloody nose, transient diabetes insipidus, cranial nerve damage, hyponatremia and CSF leaks. Surgical ablation is usually successful in rapidly reducing tumor size, inhibiting growth hormone secretion and alleviating some symptoms. Administration of somatostatin receptor ligands, dopamine agonists or a growth hormone receptor antagonist and gland irradiation may be used for tumor regression or as a treatment option for patients who are not surgical candidates. 33  Anesthetic Implications of Acromegaly Preanesthetic assessment of patients with acromegaly should include a careful examination of the airway. Facial deformities and the large nose may hamper adequate fitting of an anesthesia mask. Endotracheal intubation may be a challenge because of the patient’s large and thick tongue (macroglossia), prognathism, enlarged thyroid gland, hypertrophy and distortion of the epiglottis, and general soft tissue overgrowth in the upper airway. Subglottic narrowing and vocal cord enlargement may dictate the use of a smaller-diameter endotracheal tube. Nasotracheal intubation should be avoided or approached cautiously because of possible turbinate enlargement. Preoperative dyspnea, stridor, or hoarseness should alert the anesthetist to airway involvement. Indirect laryngoscopy, lateral neck radiographs, and computed tomography (CT) of the neck may be performed for thorough assessment. If difficulties in maintaining an adequate airway are anticipated, fiberoptic intubation in an awake patient is of proven value. A surgeon should be on hand and equipment for tracheostomy available if airway changes are advanced. Pre anesthetic assessment of patients with acromegaly should include a careful examination of the airway. Facial deformities and a large nose may make it difficult to find an anesthetic mass that will properly fit the patient. Endotracheal intubation may be challenged because of the patient's large or thick tongue, pragmatism, enlarged thyroid gland hypertrophy and distortion of the epiglottis and general soft tissue overgrowth in the upper airway. Subglottic narrowing and vocal cord enlargement may dictate the use of a smaller diameter endotracheal tube, but be careful to ensure that you still can achieve adequate tidal volume and ventilation. Nasal tracheal intubation should be avoided or approached very cautiously because of the possibility of terminate enlargement. The occurrence of Mallanpati 3 and 4 grades is higher in patients with acromegaly and the incidence of difficult intubations may be 4 to 5 times higher than patients without acromegaly. Pre operative dyspnea, stridor and hoarseness should alert the anesthetist to airway involvement. Indirect laryngoscopy, lateral neck radiographs and CTs of the neck may be performed for a more thorough assessment before taking the patient back to the operating room. Airway adjuncts should be readily available during the induction of anesthesia, as well as additional team members if needed. If difficulties in maintaining an adequate airway are anticipated, optically guided intubation, or fiber optic guided intubation in the awake patient is the proven safest road to take. A surgeon should be on hand and equipment for a tracheostomy available if airway challenges are encountered when trying to 34 secure the airway. 34  Anesthetic Implications of Acromegaly Arthropathy affects approximately 75% of acromegaly patients. Overgrowth of vertebrae may cause kyphosis and osteoarthritis and may make central neuraxial anesthesia a challenge. More than 60% of patients with acromegaly have sleep apnea. Predisposed to airway obstruction Cardiomyopathy, coronary artery disease, and hypertension in acromegalic patients warrants a thorough preanesthetic cardiac evaluation. Hyperglycemia is common - monitor of blood glucose levels. Stress-level glucocorticoid therapy may be indicated to address any impairment of the adrenal axis. Entrapment neuropathies, such as carpal tunnel syndrome, are common in patients with acromegaly. Hypertrophy of the carpal ligament may cause inadequate ulnar artery flow, which should be factored into any decision to place an arterial catheter. Arthropathy affects approximately 75% of patients that have acromegaly. Overgrowth of vertebrae may cause kyphosis and osteoarthritis, making it more challenging to perform spinals and epidurals. More than 60% of patients with acromegaly also have sleep apnea. They are predisposed for airway obstruction, leading to difficult masking and intubation. Cardiomyopathy, coronary disease and hypertension in patients with acromegaly warrants a very thorough pre anesthetic cardiac evaluation. Hyperglycemia is common, so you should be checking blood glucose levels in pre op, as well as throughout the case. Stress level glucocorticoid therapy may be indicated to address any impairment of the adrenal axis. Entrapment neuropathy, such as carpal tunnel syndrome, are common in patients with acromegaly. It's important to ask them about such syndromes beforehand and document those in your anesthetic record. Hypertrophy of the carpal ligaments may cause inadequate ulnar artery flow, which should be a factor into the decision when you're placing the arterial catheter. Make sure for these patients, if they do have any of these hypertrophies in their hands, that you are doing a true Allen test to ensure that they have adequate blood supply. 35  Posterior Pituitary Antidiuretic Hormone (ADH) Vasopressin Controls water reabsorption Causes vasoconstriction at high concentrations Oxytocin Stimulates contraction of myoepithelial cells of the breast for milk ejection during lactation Powerfully stimulates uterine smooth muscle contraction during labor Leaving the anterior pituitary and going to the posterior pituitary. The posterior pituitary lobe secretes two important peptide hormones, antidiuretic hormone known as vasopressin and oxytocin. Oxytocin and ADH are almost identical structurally. However, they have very different actions. ADH controls water reabsorption in the kidneys as a major regulator of serum osmolarity. It produces vasoconstriction at high levels, hence the names vasopressin. Oxytocin stimulates contraction of the myoepithelial cells of the breast for milk ejection during lactation. It also powerfully stimulates uterine smooth muscle contraction during delivery of the baby at the end of gestation. Oxytocin and its derivatives are used clinically for inducing labor and decreasing postpartum bleeding. 36  Posterior Pituitary Communicates with the hypothalamus through a neural pathway. Hormones are synthesized within 2 large nuclei in the hypothalamus Supraoptic nucleus ADH Paraventricular nucleus Oxytocin In contrast to the anterior pituitary lobe, which communicates with the hypothalamus via a vascular system, the posterior pituitary lobe communicates with the hypothalamus through a neural pathway. Also, unlike the anterior pituitary hormones, posterior pituitary hormones are not synthesized within the pituitary gland itself, but rather within the two large nuclei of the hypothalamus, the supraoptic nuclei and the periventricular nucleus. ADH is chiefly synthesized in the supraoptic nucleus and oxytocin in the paraventricular nucleus, as shown in the picture on the right, nerve fibers arising from these hypothalmic nuclei transport ADH and oxytocin down the pituitary stock by axoplasmic flow to the posterior pituitary lobe. There, the hormones are stored in secretory granules at the nerve terminals. With proper excitation, nerve impulses originating in the cell bodies of the super optic or paraventricular nucleus are transmitted down the pituitary stock and stimulate the release of ADH or oxytocin from the posterior pituitary lobe. The hormones then diffuse into nearby blood vessels and are transported to their distant target sites. 37  The body’s principal preserver of water balance 3 major types of Vasopressin V1 Antidiuretic Facilitates vasoconstriction V2 Hormone Facilitates water reabsorption in the renal tubules V3 Stimulation modulates corticotrophin secretion ADH is the body's principal preserver of water balance. ADH acts on specific receptors on the distal tubule and medullary collecting ducts of the kidney to increase the absorption of solute free water through water channels called Aquaporins. Without ADH, the collecting ducts are impermeable to water reabsorption. Water loss in the urine is excessive and serious dehydration and hypernatremia results. The role of thirst, vasopressin and renal response conserves water in the body and supports normal body fluid osmolarity. The three major types of vasopressin receptors have been identified and named v1 v2 and v3. Activation of the v1 receptor causes vasoconstriction. V2 receptors mediate water reabsorption in the renal tubules, and v3 receptors are found within the central nervous system, and their stimulation causes corticotropin secretion. 38  Antidiuretic Hormone Functions Acts primarily to reabsorb water High levels of ADH stimulate V1 receptors = potent vasoconstriction Use for catecholamine-resistant vasodilatory shock, hemorrhage, sepsis Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) A synthetic arginine analog of ADH and a selective V2 agonist, increases circulating levels of von Willebrand factor and factor VIII. May be used to reverse coagulopathy associated with hemophilia A, the coagulopathy of renal failure, and platelet adhesion defects such as von Willebrand disease ADH acts primarily to reabsorb water, increasing urine osmolarity, decreasing serum osmolarity and increasing blood volume. Additionally, high levels of ADH stimulate the v1 receptors and cause potent systemic vasoconstriction. ADH induced vasoconstriction of vascular beds has been used to control catecholamine resistant vasoplegic syndrome, hemorrhage and sepsis. Desmopressin, also known as DDAVP, is a synthetic arginine analog to ADH, and it's also a selective v2 agonist, it increases the circulating levels of von Willebrand factor and factor eight. In addition to effectively treating ADH deficiency, DDAVP may be used to reverse coagulopathy associated with hemophilia A, the coagulopathy of renal failure and platelet adhesion defects such as von Willebrand disease. 39  Stimulators of ADH Action of Release Increased plasma Na+ ion concentration Increased serum osmolarity Decreased blood volume Decreased blood pressure Smoking (nicotine) Stress Nausea Vasovagal reaction Medications Angiotensin II Positive pressure ventilation Consistent with its role of maintaining normal fluid of homeostasis, ADH is secreted in response to an increase in plasma osmolarity, or plasma sodium ion concentration, a decrease in blood volume or a decrease in blood pressure. The osmolarity of body fluids is the main variable controlling ADH secretion, repeat it one more time. The osmolarity of body fluids is the main variable controlling ADH secretion. Serum osmolarity changes are sensed by hypothalamic osmoreceptors, which in turn alter ADH synthesis and secretion. Increased plasma osmolarity initiates signals in the hypothalamic osmoreceptors that cause ADH release from the pituitary gland. ADH in return, enhances renal tubular water reabsorption, dilutes the extracellular fluid and restores normal osmotic composition. On the other side, water ingestion, which would be decreasing plasma osmolarity, suppresses the osmoreceptor signals for ADH release. Thirst provides a second line of defense in water balance as well. A 10 to 20% decrease in blood volume or blood pressure will provoke ADH release. Changes in blood volume are sensed in peripheral baroreceptors and atrial stretch receptors. When these baroreceptors sense under filling, indicating volume depletion, they transmit afferent signals through vagal or vosopharyngeal nerves to the hypothalamus. The hypothalamus responds by increasing ADH synthesis and stimulating ADH release. Sometimes this can go as high as 50 times the normal rate of ADH release. ADH secretion also can be stimulated by nausea, vomiting, acute 40 hypoglycemia and glucocorticoid deficiency. Emetic stimuli are especially potent, since they typically elicit an immediate increase 50 to 100 fold in plasma ADH, even when nausea is not associated with vomiting, just the sense of feeling nauseated, causes this huge increase in ADH plasma levels. Common perioperative conditions such as stress, nausea, vomiting, hemorrhage, hypotension and various drugs can all stimulate ADH release. On the other hand, positive pressure ventilation, which obviously would be occurring in the operating room, enhances ADH release by reducing central blood volume. Think again about those baroreceptors, right? You're decreasing pressure, they're going to sense that they're going to trigger to the hypothalamus to increase their ADH secretion. The mild hyponatremia, sometimes observed post operatively, may be at least partially explained based on ADH action. So here you can see a list of all the simulators of ADH release. Go through these. Think about how those are brought up, and what times during the intraoperative period or pre- op, post- op, when they would be potential players of causing the ADH release. 40  Diabetes Insipidus (DI) A disorder characterized by the excretion of excessively large amounts of dilute urine Caused by a deficiency of ADH or an inability of the kidneys to respond to ADH 2 Types Neurogenic/Central DI Nephrogenic DI Inadequate ADH secretion from the posterior pituitary lobe, or the inability of the renal collecting Doctor receptors to respond to ADH is called diabetes insipidus. Decreased ADH synthesis, transport or release from the posterior pituitary produces neurogenic or sometimes called Central DI, diabetes insipidus. Renal collecting duct resistance to vasopressin is termed nephrogenic diabetes insipidus. Both forms of DI are characterized by the production of abnormally large volumes of dilute urine and a continuous thirst. 41  Diabetes Insipidus (DI) Common causes of neurogenic/central DI: The hallmark of DI is the excretion of abnormally Surgery around the neurohypophysis large volumes of dilute urine (polyuria). Meningitis/encephalitis Pituitary lesions The inability to produce concentrated urine Brain tumors results in dehydration and hypernatremia. Closed head trauma The syndrome is characterized by: Common causes of nephrogenic DI: low urine osmolarity (